I noted just last week the latest review by Drs Newman and Cragg citing that nature remains the source of 70% of prescription drugs. Wall Street Journal medical reporter Ron Winslow took his turn yesterday contributing to the paper’s new HealthBlog from New Orleans, site of the American College of Cardiology meeting.

Turns out that a semi-synthetic analog of a compound derived from the bark of Australian magnolia may enhance anti-clotting therapy following stent implants without increasing bleeding risks. The parent molecule and the analog tested in this trial act as antagonists, or blockers, of the thrombin receptor on platelets known as PAR-1. As Winslow reports,

Schering-Plough scientists fashioned a molecule based on himbacine that could be taken as a pill. Results from a mid-stage study presented at the ACC showed the drug in various doses caused no increase in bleeding among 573 patients with newly implanted stents when it was added to their regimen of two other anti-clotting agents-Sanofi-Aventis and Bristol-Myers Squibb’s Plavix and good old aspirin. Patients were monitored for 60 days.

The clinical test also uncovered a provocative, though statistically unproved, reduction of serious problems for patients taking the drug. A 40 milligram dose of it each day cut deaths, heart attacks and hospitalizations for chest pain or additional artery-clearing procedures by 46% reduction-to 4.6% of patients taking the pill vs. 8.6% for those who didn’t get it.

The regulation of blood clotting, called hemostasis, is a true wonder of the human body. We have evolved an intricately controlled system that must keep our blood flowing freely but that also must be prepared at an instant’s notice to stop bleeding when cuts or trauma breech the vasculature. People who have already had blood clots in critical vessels are predisposed to second clots and usually continue to take drugs to prevent these secondary blockages. Those who have bare-metal or drug-eluting stents implanted to keep these vessels open also must take anticoagulant therapy, often for the rest of their lives. But a risk of those drugs is that, in rare instances, they can also increase the risk of bleeding. Successful manipulation of this balance is one of the miracles of modern pharmacology (and I’m not a cardiovascular pharmacologist).
Winslow is a veteran reporter, so he is wise to temper his post with the caution that these results are only from a Phase 2 study, the clinical trial stage where an agent is first tested for any indication of effectiveness:

We at Health Blog are duty bound to say that the drug’s promise in mid-stage, or Phase II, studies is no guarantee that it will make it to market. Just ask Pfizer about its busted bet on torcetrapib, a good-cholesterol booster, which sailed through Phase II only to crash in Phase III. More on that tomorrow.

But pivotal, large-scale tests of the Schering-Plough medicine are in the works, and the drug is moving up the ranks of closely-watched heart medicines in development. Success in the next stage of clinical testing would put the drug, now known only as SCH 530348, in contention for a big chunk of the growing, multi-billion dollar market for medicines to prevent clots.

For further information, the press release is here with much more detail on the study design and endpoints monitored. Similar to Winslow’s caution, Terra Sig readers interested in anti-coagulant therapy should note also that this is a meeting abstract and not yet a peer-reviewed publication.